This is a five year RO1 proposal to study the role of FGFR3 and FGF9 in bone development. The objectives of this proposal are to determine how FGFR3 regulates chondrogenesis and how it interacts with other signalling molecules thought to be important for endochondral ossification and to identify the physiological ligands that activate FGFR3 in vivo during endochondral ossification. The first aim will explore the expression of FGFR3 in the growth plates of normal mice using a transgenic mouse in which the LacZ gene is under control of the FGFR3 promoter and by immunohistochemistry. The second aim explores whether ligand affinity is altered by the Ach and TD mutation and whether chondrocyte gene activity is altered in culture. The third aim will ascertain by RT-PCR which FGFs are present in the adult growth plate. In the fourth aim it is proposed to complete a catalog of the expression of FGF9 by organ system ISH, RNAse protection assay, immunolocalization, FGF9-LacZ transgenic and the FGF9 gene structure will be completed.